NM_004278.4:c.424C>A
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM1BP4_StrongBP6BS1BS2
The NM_004278.4(PIGL):c.424C>A(p.Leu142Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00584 in 1,611,252 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004278.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00481 AC: 732AN: 152164Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00509 AC: 1280AN: 251468Hom.: 7 AF XY: 0.00520 AC XY: 707AN XY: 135910
GnomAD4 exome AF: 0.00595 AC: 8681AN: 1458970Hom.: 41 Cov.: 28 AF XY: 0.00586 AC XY: 4255AN XY: 726104
GnomAD4 genome AF: 0.00481 AC: 732AN: 152282Hom.: 6 Cov.: 32 AF XY: 0.00447 AC XY: 333AN XY: 74448
ClinVar
Submissions by phenotype
not provided Benign:3
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PIGL: BP4, BS2 -
CHIME syndrome Uncertain:1Benign:1
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Coloboma, Congenital Heart Disease, Ichthyosiform Dermatosis, Intellectual Disability, and Ear Anomalies (CHIME) Syndrome Uncertain:1
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not specified Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at